Specialized functions and sexual dimorphism explain the functional diversity of the myeloid populations during glioma progression

Autor: Natalia Ochocka, Pawel Segit, Kamil Wojnicki, Salwador Cyranowski, Julian Swatler, Karol Jacek, Wiesława Grajkowska, Bozena Kaminska
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 1, Pp 111971- (2023)
Druh dokumentu: article
ISSN: 2211-1247
80337392
DOI: 10.1016/j.celrep.2022.111971
Popis: Summary: Malignant gliomas are aggressive, hard-to-treat brain tumors. Their tumor microenvironment is massively infiltrated by myeloid cells, mostly brain-resident microglia, bone marrow (BM)-derived monocytes/macrophages, and dendritic cells that support tumor progression. Single-cell omics studies significantly dissected immune cell heterogeneity, but dynamics and specific functions of individual subpopulations were poorly recognized. We use Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) to precisely dissect myeloid cell identities and functionalities in murine GL261 gliomas. We demonstrate that the diversity of myeloid cells infiltrating gliomas is dictated by cell type and cell state. Glioma-activated microglia are the major source of cytokines attracting other immune cells, whereas BM-derived cells show the monocyte-to-macrophage transition in the glioma microenvironment. This transition is coupled with a phenotypic switch from the IFN-related to antigen-presentation and tumor-supportive gene expression. Moreover, we found sex-dependent differences in transcriptional programs and composition of myeloid cells in murine and human glioblastomas.
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